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Abstracts This study constructs a indicators system of urban ecological resilience based on “resistance-adaptation-recovery”, and measures the level of cities within the Yangtze River Economic Belt and the Yellow River Basin from 2006 to 2021. Utilizing the Dagum Gini coefficient, traditional and spatial kernel density methods, and geographical detector, the study comprehensively analyzes the spatiotemporal evolution and causes of urban ecological resilience in these regions across multiple dimensions. Furthermore, it explores different paths for enhancing resilience of the two regions. The results indicate: (1) The urban ecological resilience level of the Yangtze River Economic Belt is significantly lower than that of the Yellow River Basin, yet it exhibits a faster growth rate. Both regions show a distribution characterized by “higher in the east, lower in the west”. (2) The overall internal differences between the two regions show a downward trend. The Yangtze River Economic Belt exhibited more pronounced spatial imbalances compared to the Yellow River Basin; however, since 2011, this trend has reversed. (3) The overall resilience in both regions is improving, and the absolute gap is gradually narrowing, showing a significant trend towards polarization in terms of evolutionary features. Cities with lower resilience levels demonstrate increased upward mobility, while cities with higher levels exhibit low mobility or even a decline. (4) Differences in restoration and adaptative capabilities are the principal intrinsic factors affecting the resilience differences between the two regions, whereas variations in economic development and capital efficiency serve as important extrinsic factors determining their spatiotemporal evolution differences. (5) Increasing investment in green technologies, promoting industrial low-carbon transformations, encouraging social green investments, and strengthening green technological innovations are crucial strategies for enhancing urban ecological resilience in both regions. Meanwhile, optimizing open channels significantly improves the urban ecological resilience in the Yellow River Basin.

Abstract Background The prognosis of advanced gastric cancer (AGC) is relatively poor, and long-term survival depends on timely intervention. Currently, predicting survival rates remains a hot topic. The application of radiomics and immunohistochemistry-related techniques in cancer research is increasingly widespread. However, their integration for predicting long-term survival in AGC patients has not been fully explored. Methods We Collected 150 patients diagnosed with AGC at the Affiliated Zhongshan Hospital of Dalian University who underwent radical surgery between 2015 and 2019. Following strict inclusion and exclusion criteria, 90 patients were included in the analysis. We Collected postoperative pathological specimens from enrolled patients, analyzed the expression levels of MAOA using immunohistochemical techniques, and quantified these levels as the MAOAHScore. Obtained plain abdominal CT images from patients, delineated the region of interest at the L3 vertebral body level, and extracted radiomics features. Lasso Cox regression was used to select significant features to establish a radionics risk score, convert it into a categorical variable named risk, and use Cox regression to identify independent predictive factors for constructing a clinical prediction model. ROC, DCA, and calibration curves validated the model’s performance. Results The enrolled patients had an average age of 65.71 years, including 70 males and 20 females. Multivariate Cox regression analysis revealed that risk (P = 0.001, HR = 3.303), MAOAHScore (P = 0.043, HR = 2.055), and TNM stage (P = 0.047, HR = 2.273) emerged as independent prognostic risk factors for 3-year overall survival (OS) and The Similar results were found in the analysis of 3-year disease-specific survival (DSS). The nomogram developed could predict 3-year OS and DSS rates, with areas under the ROC curve (AUCs) of 0.81 and 0.797, respectively. Joint calibration and decision curve analyses (DCA) confirmed the nomogram’s good predictive performance and clinical utility. Conclusion Integrating immunohistochemistry and muscle fat features provides a more accurate prediction of long-term survival in gastric cancer patients. This study offers new perspectives and methods for a deeper understanding of survival prediction in AGC.

Abstract Background The prevalence of understory removal and anthropogenic nitrogen (N) deposition has significantly altered the ecological processes of forest ecosystems at both regional and global scales. However, it remains a pressing challenge to understand how N deposition and understory removal affect leaf nutrient dynamics, nutrient resorption, litter decomposition, and their linkages for better managing forest ecosystems under nutrient imbalances induced by N enrichment. To address this research gap, a field manipulation experiment was carried out in a subtropical Cunninghamia lanceolata plantation with four treatments including: control (CK), canopy N addition (CN), understory removal (UR), and canopy N addition plus understory removal (CN × UR). Green and senesced leaf N and phosphorus (P) concentrations, N and P resorption efficiencies, litter decomposition, and their correlations were measured. Results The results revealed that the average N concentrations of green early and late leaves in UR were increased by 6.61 and 18.89% compared to CK. UR had the highest whereas CN had the lowest P concentrations in green leaves across the two sampling seasons. Following this, UR, leaf type, season, and their interactions significantly affected leaf N, P, and N:P (P

Abstract Ginseng rusty root symptoms (GRS) is a primary disease of ginseng, which seriously decreases the yield and quality of ginseng and causes enormous losses to ginseng production. GRS prevention and control is still challenging due to its unclear etiology. In this study, the phloem tissue of healthy Panax ginseng (AG), the nonred tissue of the phloem epidermis around the lesion (BG), and the red lesion site tissue of GRS (CG) were extracted for mRNA transcriptomic analysis; 35,958 differentially expressed genes (DEGs) were identified and were associated with multiple stress resistance pathways, reactive oxygen species (ROS), and iron ion binding. Further study showed that the contents of O2•‐, H2O2, and malondialdehyde (MDA) were significantly increased in BG and CG tissues. Under anaerobic conditions caused by excessive soil moisture, the overproduction of ROS destroys cell membranes, simultaneously converting Fe2+ to Fe3+ and depositing it in the cell wall, which results in GRS, as evidenced by the success of the GRS induction test.

Abstract In fatigue data analysis, fitting accurate P-S-N curve is problematic if only a small number of specimen is available, especially to evaluate the relationship between the stress level and the standard deviation. This paper proposes a sample information reconstruction method that can effectively solve this problem. Based on this method and the life equivalent principle, a new maximum likelihood method (which is abbreviated to improved maximum likelihood method) is proposed for P-S-N curve fitting. T-joint specimens of Q450NQR1 steel were fabricated and tested, then the P-S-N curves was fitted by the improved maximum likelihood method, least square method, maximum likelihood method, standard BS7608 and standard IIW. Finally, P-S-N curves by three methods and two standards are compared and analyzed. The results show that the relevant parameters of the P-S-N curve with 99.9% survival probability fitted by the improved maximum likelihood method are similar to those in the two standards, and it is indicated that the improved maximum likelihood method is a better way for P-S-N curve fitting with the small number of fatigue test specimens.

Abstract Purpose This study aims to investigate the predictive value of the combined index smni(skeletal muscle index (SMI)-prognostic nutrition index(PNI)) for the postoperative survival of patients with advanced gastric cancer(AGC). Methods 650 patients with AGC from two centers (290 cases from the First Affiliated Hospital of Dalian University and 360 points from the Fujian Medical University Union Hospital) were selected as the study subjects based on unified screening criteria. Clinical data, preoperative abdominal CT images, results of hematology-related examinations, tumor-related characteristics, and surgical and follow-up data of the patients were collected and organized. The L3 vertebral level muscle area was measured using computer-assisted measurement techniques, and the skeletal muscle index(SMI) was calculated based on this measurement. The prognostic nutrition index (PNI) was calculated based on serum albumin and lymphocyte count indicators. The Kaplan-Meier survival analysis of data from the First Affiliated Hospital was used to determine that SMI and PNI are significantly correlated with the postoperative survival rate of patients with advanced gastric cancer. Based on this, a novel combined index smni was fitted and stratified for risk. Cox proportional hazards regression analysis was used to determine that the index smni is an independent prognostic risk factor for patients with AGC after surgery. The ROC curve was used to describe the predictive ability of the new combined index and its importance and predictive power in predicting postoperative survival of patients with AGC, which was verified in the data of Fujian Medical University Union Hospital. Result The Kaplan-Meier curve analysis of the combined indicator smni Is clearly associated with long-term survival(3-year OS (P

The management of understory vegetation and anthropogenic nitrogen (N) deposition has significantly resulted in a nutrient imbalance in forest ecosystems. However, the effects of canopy nitrogen addition and understory vegetation removal on N transformation processes (mineralization, nitrification, ammonification, and leaching) along with seasonal variations (spring, summer, autumn, and winter) remain unclear in subtropical forests. To fill this research gap, a field manipulation experiment was conducted with four treatments, including: (i) CK, control; (ii) CN, canopy nitrogen addition (25 kg N ha−1 year−1); (iii) UR, understory vegetation removal; and (iv) CN+UR, canopy nitrogen addition plus understory vegetation removal. The results revealed that CN increased net mineralization and nitrification by 294 mg N m−2 month−1 in the spring and 126 mg N m−2 month−1 in the winter, respectively. UR increased N mineralization and nitrification rates by 618 mg N m−2 month−1 in the summer. In addition, CN effectively reduced N leaching in the spring, winter, and autumn, while UR increased it in the spring and winter. UR increased annual nitrification rates by 93.4%, 90.3%, and 38.9% in the winter, spring, and summer, respectively. Additionally, both net N ammonification and annual nitrification rates responded positively to phosphorus availability during the autumn. Overall, UR potentially boosted nitrification rates in the summer and ammonification in the spring and winter, while CN reduced N leaching in the spring, winter, and autumn. Future research should integrate canopy nitrogen addition, understory vegetation removal, and phosphorus availability to address the global N deposition challenges in forest ecosystems.

Abstract Projection of future dry‐wet evolution is essential for making long‐term regional climate adaptation strategies. In this study, the projection of regional dry‐wet evolution is conducted with a careful consideration on uncertainty attribution. The Evaporative Stress Index (ESI) is adopted due to its physical mechanisms for taking evaporative demand into account. A three‐dimensional framework is constructed for quantifying the range of uncertainty of the ESI in which six Global Climate Models (GCMs) in Coupled Model Intercomparison Project 6 (CMIP6), three latest Shared Socioeconomic Pathway (SSP) scenarios, and six Potential Evapotranspiration Models (PETMs) are used. The framework provides 108 different ESI simulations for two future periods: 2041–2070 (mid‐future) and 2071–2100 (far‐future). An agglomerative‐hierarchical clustering method and the Analysis of Variance methodology are employed to evaluate the relative contribution of each uncertainty source. The region of Northwest China is used as a case to illustrate the effectiveness of the proposed framework. The results indicate that most of the parts in Northwest China would experience dry mitigation in both mid‐future and far‐future periods. Projected ESI by PM[CO2] model and ACCESS‐ESM1‐5 suggestes a higher tendency for dry mitigation. Hierarchical clustering analysis of the 108 sets of ESI predictions indicate that most clusters are dominated by GCM forcing, and one cluster is dominated by the SSP1‐2.6 scenario. Furthermore, GCM‐related uncertainty′s relative contribution to the total projection uncertainty is the greatest, with an average value of 49.98% in the far future (i.e., 2071–2100 s). Although the contribution of SSP uncertainty is smaller (21.68%−28.43%), it increases in far‐future over mid‐future. The case study indicates that the large scale ensemble prediction of ESI and its uncertainty analysis provide a more comprehensive data set on climate change and help water managers to gain in‐depth understanding of future trends of drought projections.

In this paper, we propose a sensorless control strategy for permanent magnet synchronous motors (PMSMs) based on an adaptive-gain sliding mode observer (ASMO) with precise compensation. Firstly, the observer adopts a saturation function with a continuous boundary layer as the switching function to avoid the delay effect of the low-pass filter. In addition, the adaptive-gain method is designed based on a conventional sliding mode observer (SMO) with constant-gain and a saturation function. The adaptive-gain mathematical model is simplified by establishing a nonlinear feedback channel of an SMO. Secondly, in order to improve the practicability and facilitate debugging, the explicit stability condition of an ASMO is deduced according to Lyapunov’s second method. According to the proposed adaptive method, the chattering caused by the mismatch of the sliding-mode gain is suppressed, and the observable speed range is also improved. Thirdly, the position estimation delay problem of an SMO with a continuous switching function is analyzed in detail from the perspective of frequency characteristics. Then, a precise compensation method is proposed for the delay problem, which greatly improves the position estimation accuracy and the control performance. Finally, the correctness of the theory and the feasibility of the ASMO with precise compensation for the sensorless control of PMSMs are verified by experiments.

Abstract Purpose Lung metastasis (LM) is one of the most frequent distant metastases of thyroid cancer (TC). This study aimed to develop a machine learning algorithm model to predict lung metastasis of thyroid cancer for providing relative information in clinical decision‐making. Methods Data comprising of demographic and clinicopathological characteristics of patients with thyroid cancer were extracted from the National Institutes of Health (NIH)’s Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015, which is employed to develop six machine learning algorithm models support vector machine (SVM), logistic regression (LR), eXtreme gradient boosting (XGBoost), decision tree (DT), random forest (RF), and k‐nearest neighbor (KNN). Compared and evaluated models by the following indicators: accuracy, precision, recall rate, F1‐score, the area under the ROC curve (AUC) value and Brier score, and interpreted the association between clinicopathological characteristics and target variables based on the best model. Results Nine thousand nine hundred and fifty patients were selected, which including 212 patients (2.1%) with lung metastasis, and 9738 patients without lung metastasis (97.9%). Multivariate logistic regression showed that age, T stage, N stage, and histological type were independent factors in TC with LM. Evaluation indicators of the best model‐ RF were as following: accuracy (0.99), recall rate (0.88), precision (0.61), F1‐score (0.72), AUC value (0.99), and the Brier score (0.016). Conclusion RF learning model performed better and can be applied to forecast lung metastasis of thyroid cancer, and offer valuable and significant reference for clinicians' decision‐making in advance.

Summary: Here, we report the scalable fabrication of 2i-functionalized micro-pyramid-array (μPyA/+2i) inserts for use in commercial multi-well plates, as the alternative cultivation platform for maintaining long-term self-renewal and pluripotency of multiple mESCs and mouse induced pluripotent stem cells. Relevant evidence including cell morphology characterization increased alkaline phosphatase activity, high expression of mESC self-renewal markers, decreased levels of differentiation-associated markers, and high proportion of self-renewal marker cells are provided. Further studies demonstrated that μPyA/+2i could cause a higher cell density in mESC colony, and induce gene expression changes. Subsequent studies showed that μPyA/+2i can influence the cytoskeleton and promote cell adhesion through Cldn-7 upregulation. In summary, these μPyA/+2i inserts offer flexible and gelatin-free micro-envriomnets to maintain long-term self-renewal and pluripotency of mESCs. Enabled by the microstructured inserst, the facile stem cell manipulation and transfer among culture dishes will broaden stem cells both in routine and translational applications.

Assessing how fruit tree expansion and climate variability affect hydrological components (e.g., water yield, surface runoff, underground runoff, soil water, evapotranspiration, and infiltration) at different spatial scales is crucial for the management and protection of watersheds, ecosystems, and engineering design. The Jiujushui watershed (259.32 km2), which experienced drastic forest changes over the past decades, was selected to explore the response mechanisms of hydrological components to fruit tree expansion and climate variability at different spatial scales (whole basin and subbasin scale). Specifically, we set up two change scenarios (average temperature increase of 0.5°C and fruit tree area expansion of 18.97%) in the SWAT model by analyzing historical data (1961∼2011). Results showed that climate change reduced water yield, surface runoff, and underground runoff by 6.75, 0.37, and 5.91 mm, respectively. By contrast, the expansion of fruit trees increased surface runoff and water yield by 2.81 and 4.10 mm, respectively, but decreased underground runoff by 1 mm. Interestingly, the sub-basins showed different intensities and directions of response under climate change and fruit tree expansion scenarios. However, the downstream response was overall more robust than the upstream response. These results suggest that there may be significant differences in the hydrological effects of climate change and fruit tree expansion at different spatial scales, thus any land disturbance measures should be carefully considered.

Objective: Papillary thyroid carcinoma (PTC) accounts for 80% of thyroid malignancy, and the occurrence of PTC is increasing rapidly. The present study was conducted with the purpose of identifying novel and important gene panels and developing an early diagnostic model for PTC by combining artificial neural network (ANN) and random forest (RF).Methods and results: Samples were searched from the Gene Expression Omnibus (GEO) database, and gene expression datasets (GSE27155, GSE60542, and GSE33630) were collected and processed. GSE27155 and GSE60542 were merged into the training set, and GSE33630 was defined as the validation set. Differentially expressed genes (DEGs) in the training set were obtained by “limma” of R software. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis as well as immune cell infiltration analysis were conducted based on DEGs. Important genes were identified from the DEGs by random forest. Finally, an artificial neural network was used to develop a diagnostic model. Also, the diagnostic model was validated by the validation set, and the area under the receiver operating characteristic curve (AUC) value was satisfactory.Conclusion: A diagnostic model was established by a joint of random forest and artificial neural network based on a novel gene panel. The AUC showed that the diagnostic model had significantly excellent performance.

The literature on corruption is extensive. However, specific effects of corruption on industrial structure upgrade have received little attention in the context of China. Therefore, following the concept of organizational performance and social capital theory, a number of panel models are developed to explore how different institution domains (i.e., government’s willingness to reform, business ownership structure, and government-business collusion) moderate the effect size of corruption on upgrading the industrial structure in China. The results are generally robust after endogeneity corrections, and suggest that the effect size of corruption on the industrial structure upgrade is evidently moderated by willingness to reform and ownership structure, but government-business collusion does not appear to have a similar effect. These findings explain the variation in the corruption-performance link, and provide a novel perspective for policy makers and regulators to understand the evolutionary path of corruption within the process of economic transition in China. A local government must thoroughly understand the dynamics of an industrial structure upgrade and acquire competencies and knowledge about when the effect of corruption reaches its inflection point and how its downside can be alleviated by placing specific formal and informal institutional reforms.

Freezing stress is the main factor affecting the normal growth and distribution of plants. The safe overwintering of a perennial deciduous plant is a crucial link to ensuring its survival and yield. However, little is known about the molecular mechanism of its gene regulation metabolites as related to its freeze-tolerance. In order to enhance our comprehension of freeze-tolerance metabolites and gene expression in dormant apple trees, we examined the metabolic and transcriptomic differences between ‘Ralls’ and ‘Fuji’, two apple varieties with varying degrees of resistance to freezing. The results of the freezing treatment showed that ‘Ralls’ had stronger freeze-tolerance than ‘Fuji’. We identified 302, 334, and 267 up-regulated differentially accumulated metabolites (DAMs) and 408, 387, and 497 down-regulated DAMs between ‘Ralls’ and ‘Fuji’ under −10, −15, and −20 °C treatment, respectively. A total of 359 shared metabolites were obtained in the upward trend modules, of which 62 metabolites were associated with 89 pathways. The number of up-regulated genes accounted for 50.2%, 45.6%, and 43.2% of the total number of differentially expressed genes (DEGs), respectively, at −10, −15, and −20 °C. Through combined transcriptome and metabolome analysis, we identified 12 pathways that included 16 DAMs and 65 DEGs. Meanwhile, we found that 20 DEGs were identified in the phenylpropanoid biosynthesis pathway and its related pathways, involving the metabolism of p-Coumaroyl-CoA, 7, 4′-Dihydroxyflavone, and scolymoside. These discoveries advance our comprehension of the molecular mechanism underlying apple freeze-tolerance and provide genetic material for breeding apple cultivars with enhanced freeze-tolerance.

With the increasing global demand for renewable energy (RE), the growing share of new energy sources has become an inevitable trend. However, due to the uncertainty and fluctuation of renewable energy generation, this poses challenges to the stability of the power system. To mitigate the volatility of wind power output, ensure reliable power supply, and improve energy storage utilization, shared energy storage (SES) can be deployed in renewable energy bases (REBs) to alleviate the pressure on the power supply. However, electrochemical energy storage (EES) faces issues such as lifespan degradation and maintenance cost allocation. In this regard, this paper establishes an EES characterization model considering the dynamic degradation characteristics of batteries and analyzes the coupled relationship between lifespan degradation laws and key parameters in SES operation. Additionally, to assess the impact of electrochemical energy storage’s dynamic degradation characteristics on energy capacity allocation and operational strategies, an optimization model for SES in REBs is developed. Building upon this, a cost allocation mechanism is designed based on the marginal contribution in both the day-ahead and the real-time markets to address the differing demands for SES among different units within the REBs. Case studies are conducted to validate the rationality of the proposed optimization model for SES in REBs and the adaptability of the cost allocation mechanism. The results provide valuable insights for practical applications.

Forests are among the most important N pools of all terrestrial ecosystems. Elevated atmospheric N deposition in recent decades has led to increased interest in the influences of N application on forest N cycles. However, accurate assessments of N storage in forest ecosystems remain elusive. We used a 14-year experiment of a Chinese fir [Cunninghamia lanceolata (Lamb.) Hook] plantation to explore how long-term N fertilization affected N storage and recovery rates. Our study plots were located in a field that had been continuously fertilized over 14 years (2004–2017) with urea at rates of 0 (N0, control), 60 (N60, low-N), 120 (N120, medium-N), and 240 (N240, high-N) kg N hm−2a−1. Data were collected that included N content and biomass in the understory, litter, and various plant organs (i.e., leaves, branches, stems, roots, and bark), as well as soil N content and density at different depths. Results showed that the total ecosystem N storage in the N-fertilized plots was 1.1–1.4 times higher than that in the control plots. About 12.36% of the total ecosystem N was stored in vegetation (plant organs, litter, and understory) and 87.64% was stored in soil (0–60 cm). Plant organs, litter, and soil had higher N storage than the understory layer. Significantly higher plant N uptake was found in the medium-N (1.2 times) and high-N (1.4 times) treatments relative to the control. The N recovery rate of the understory layer in the N-fertilized treatments was negative and less than that in the control. Application of long-term N fertilizer to this stand led to a low N recovery rate (average 11.39%) and high loss of N (average 91.86%), which indicate low N use efficiency in the Chinese fir plantation ecosystem. Our findings further clarify the distribution of N in an important terrestrial ecosystem and improve our understanding of regional N cycles.

Abstract Nitrogen enrichment is pervasive in forest ecosystems, but its influence on understory plant communities and their stoichiometric characteristics is poorly understood. We hypothesize that when forest is enriched with nitrogen (N), the stoichiometric characteristics of plant species explain changes in understory plant diversity. A 13‐year field experiment was conducted to explore the effects of N addition on foliar carbon (C): N: phosphorus (P) stoichiometry, understory plant species richness, and intrinsic water use efficiency (iWUE) in a subtropical Chinese fir forest. Four levels of N addition were applied: 0, 6, 12, and 24 g m−2 year−1. Individual plant species were categorized into resistant plants, intermediate resistant plants, and sensitive plants based on their response to nitrogen addition. Results showed that N addition significantly decreased the number of species, genera, and families of herbaceous plants. Foliar N:P ratios were greater in sensitive plants than resistant or intermediate resistant plants, while iWUE showed an opposite trend. However, no relationship was detected between soil available N and foliar N, and soil N:P and foliar N:P ratios. Our results indicated that long‐term N addition decreased the diversity of understory plants in a subtropical forest. Through regulating water use efficiency with N addition, sensitive plants change their N:P stoichiometry and have a higher risk of mortality, while resistant plants maintain a stable N:P stoichiometry, which contributes to their survival. These findings suggest that plant N:P stoichiometry plays an important role in understory plant performance in response to environmental change of N.

Biochar can be used to address the excessive use of tetracycline and micronutrient chromium (Cr) in wastewater that potentially threatens human health. However, there is little information about how the biochar, made from different tropical biomass, facilitates tetracycline and hexavalent chromium (Cr(VI)) removal from aqueous solution. In this study, biochar was prepared from cassava stalk, rubber wood and sugarcane bagasse, then further modified with KOH to remove tetracycline and Cr(VI). Results showed that pore characteristics and redox capacity of biochar were improved after modification. KOH-modified rubber wood biochar had the highest removal of tetracycline and Cr(VI), 1.85 times and 6 times higher than unmodified biochar. Tetracycline and Cr(VI) can be removed by electrostatic adsorption, reduction reaction, π–π stacking interaction, hydrogen bonding, pore filling effect and surface complexation. These observations will improve the understanding of the simultaneous removal of tetracycline and anionic heavy metals from wastewater.

The compression tests under the unidirection for magnetorheological (MR) fluids have been studied at different compressive speeds. The results indicated that curves of compressive stress under different compression speeds at the applied magnetic field of 0.15 T overlapped well and were shown to be an exponent of about 1 of the initial gap distance in the elastic deformation region and accorded well with the description of continuous media theory. The difference in compressive stress curves increases significantly with an increasing magnetic field. At this time, the continuous media theory description could not be accounted for the effect of compressive speed on the compression of MR fluid, which seems to deviate from the Deborah number prediction under the lower compressive speeds. An explanation based on the two-phase flow due to aggregations of particle chains resulting in much longer relaxation times at a lower compressive speed was proposed to explain this deviation. The results have guiding significance for the theoretical design and process parameter optimization for the squeeze-assisted MR devices such as MR dampers and MR clutches based on the compressive resistance.

A two-layer optimization strategy for the battery energy storage system is proposed to realize primary frequency regulation of the grid in order to address the frequency fluctuation problem caused by the power dynamic imbalance between the power system and load when a large number of new energy sources are connected to the grid. An integrated control mode combining virtual sag control and virtual inertia control is proposed in the adaptive regulation layer to provide fast frequency support for the grid while effectively reducing steady-state frequency difference fluctuation. The equal consumption micro-increment criterion is used in the equalization control layer to distribute the energy output of each group while maintaining a good battery charge level. The results of the final simulation in Matlab/Simulink show that the proposed control strategy can effectively improve the system’s primary frequency regulation performance.

Abstract The deposition of reactive nitrogen (N) has substantially increased in subtropical regions due to human activities. However, the effects of long‐term N addition on the water‐use efficiency of subtropical forests are poorly understood. Here, we conducted an 11‐year experiment in a subtropical Cunninghamia lanceolate plantation with four N‐addition levels: N0, N1, N2, and N3 (equivalent to 0, 6, 12, and 24 g N m−2 year−1, respectively). A thermal dissipation probe system was used to calculate sap flow, and plant biomass carbon was assessed by field investigation. The whole‐plant water use and water‐use efficiency were estimated. In addition, the δ13C of tree rings was used to indicate the plant intrinsic water‐use efficiency. The results showed that N3 treatment significantly increased the annual sap flow velocity, especially in summer and winter. Annual water use, plant growth, and water‐use efficiency did not significantly differ among the N treatments, but water use tended to be higher in N3 treatment than in N0 treatment. Furthermore, the significant reduction of δ13C in N3 treatment than in N0 treatment supported the inference that N addition could increase water use. We conclude that long‐term addition of high levels (but not of low levels) of N increased whole‐plant water use in C. lanceolate plantations. Our findings indicate that N deposition accompanied by high temperature and drought events may negatively affect water balance in subtropical forests.

Background. The BRAF V600E mutation is an important genetic event in papillary thyroid cancer (PTC). This study aimed to provide additional information regarding the association of the BRAF V600E mutation with PTC prognosis. Methods. A retrospective single-center study based on a Chinese population was performed to analyze the association of the BRAF V600E mutation with several clinicopathological features. Kaplan–Meier survival curves and Cox proportional hazards regression analysis were applied to implement the survival analysis. Results. The BRAF V600E mutation was present in 1102 (87.7%) of the 1257 patients and was significantly associated with older age, conventional subtype, multifocality, advanced TNM stage, and a reduced prevalence of Hashimoto’s thyroiditis. The Kaplan–Meier survival curves demonstrated that the difference between the BRAF V600E-positive and BRAF V600E-negative groups was significant with a log-rank P-value of 0.048. The Cox proportional hazards regression analysis adjusted HR was 3.731 (95% CI, 1.457 to 9.554). We further demonstrated that larger tumor size (>1 cm), extrathyroidal extension (ETE), and lateral lymph node metastasis (LNM) were associated with a higher probability of PTC recurrence in patients harboring the BRAF V600E mutation. Conclusions. The BRAF V600E mutation remains an independent risk factor for PTC recurrence and may be useful for clinical decisions when it combines with some pathological factors.

Background: Progression of Alzheimer's disease is thought initially to depend on rising amyloidβ and its synaptic interactions. Transgenic mice (TASTPM; APPSwe/PSEN1M146V) show altered synaptic transmission, compatible with increased physiological function of amyloidβ, before plaques are detected. Recently, the importance of microglia has become apparent in the human disease. Similarly, TASTPM show a close association of plaque load with upregulated microglial genes. Methods: CA1 synaptic transmission and plasticity were investigated using in vitro electrophysiology. Microglial relationship to plaques was examined with immunohistochemistry. Behaviour was assessed with a forced-alternation T-maze, open field, light/dark box and elevated plus maze. Findings: The most striking finding is the increase in microglial numbers in TASTPM, which, like synaptic changes, begins before plaques are detected. Further increases and a reactive phenotype occur later, concurrent with development of larger plaques. Long-term potentiation is initially enhanced at pre-plaque stages but decrements with the initial appearance of plaques. Finally, despite altered plasticity, TASTPM have little cognitive deficit, even with a heavy plaque load, although they show altered non-cognitive behaviours. Interpretation: The pre-plaque synaptic changes and microglial proliferation are presumably related to low, non-toxic amyloidβ levels in the general neuropil and not directly associated with plaques. However, as plaques grow, microglia proliferate further, clustering around plaques and becoming phagocytic. Like in humans, even when plaque load is heavy, without development of neurofibrillary tangles and neurodegeneration, these alterations do not result in cognitive deficits. Behaviours are seen that could be consistent with pre-diagnosis changes in the human condition. Funding: GlaxoSmithKline; BBSRC; UCL; ARUK; MRC. Keywords: Alzheimer's disease, Dementia, Mouse model, Synaptic transmission, Microglia, Plaque, Neurodegeneration

Unidirectional compressive properties of magnetorheological (MR) fluids have been investigated under slow compression and constant area with different magnetic fields and different initial gap distances. Experimental tests of unidirectional compression were firstly carried out by using a commercial plate–plate rheometer. The theoretical model based on the continuous squeeze flow theory was developed to calculate the compressive stress. The comparisons between the measured and calculated compressive stresses of MR fluids were made. It showed that the compression resistance of the MR fluid in the magnetic field was much higher than that predicted by the theory. With the increasing magnetic flux density, the deviation between measured and calculated curves accelerated. Characteristics of the compressive stress variation with the reduction in gap distance have been analyzed. The structure strengthening effect induced by the chain structure aggregation in squeeze mode has been used to explain this deviation.

Abstract The homology‐independent targeted integration (HITI) strategy enables effective CRISPR/Cas9‐mediated knockin of therapeutic genes in nondividing cells in vivo, promising general therapeutic solutions for treating genetic diseases like X‐linked juvenile retinoschisis. Herein, supramolecular nanoparticle (SMNP) vectors are used for codelivery of two DNA plasmids—CRISPR‐Cas9 genome‐editing system and a therapeutic gene, Retinoschisin 1 (RS1)—enabling clustered regularly interspaced short palindromic repeats (CRISPR)‐associated protein 9 (CRISPR/Cas9) knockin of the RS1 gene with HITI. Through small‐scale combinatorial screenings, two SMNP vectors, with Cas9 and single guide RNA (sgRNA)‐plasmid in one and Donor‐RS1 and green fluorescent protein (GFP)‐plasmid in the other, with optimal delivery performances are identified. These SMNP vectors are then employed for CRISPR/Cas9 knockin of RS1/GFP genes into the mouse Rosa26 safe‐harbor site in vitro and in vivo. The in vivo study involves intravitreally injecting the two SMNP vectors into the mouse eyes, followed by repeated ocular imaging by fundus camera and optical coherence tomography, and pathological and molecular analyses of the harvested retina tissues. Mice ocular organs retain their anatomical integrity, a single‐copy 3.0‐kb RS1/GFP gene is precisely integrated into the Rosa26 site in the retinas, and the integrated RS1/GFP gene is expressed in the retinas, demonstrating CRISPR/Cas9 knockin of RS1/GFP gene.

The low-toxicity treatment of chromium-containing wastewater represents an important way of addressing key environmental problems. In this study, a core-shell structural ZIF-8@TiO2 photocatalyst was synthesized by a simple one-step hydrothermal method. The obtained composite photocatalyst possessed improved photocatalytic activity compared with TiO2. The results indicated that the optimized ZIF-8@TiO2 composite exhibited the highest removal efficiency with 93.1% of Cr(VI) after 120 min under UV-vis irradiation. The removal curves and XPS results indicated that the adsorbed Cr(VI) on the ZIF-8 during the dark process was preferentially reduced. The superior removal efficiency of ZIF-8@TiO2 is attributed to the combination of both high adsorption of ZIF-8, which attracted Cr(VI) on the composite surface, and the high separation efficiency of photo-induced electron-hole pairs. For the mixture of wastewater that contained methyl orange and Cr(VI), 97.1% of MO and 99.7% of Cr(VI) were removed after 5 min and 60 min light irradiation, respectively. The high removal efficiency of multiple pollutants provides promising applications in the field of Cr(VI) contaminated industrial wastewater treatment.

Here, a dual-modification strategy using KMnO4 (potassium permanganate) and AlCl3·6H2O (aluminum chloride, hexahydrate) as co-modifiers to improve the Cr(VI) removal capacity of K2CO3 activated biochar is introduced. As a result, the dual-modified biochar with KMnO4 and AlCl3·6H2O has the calculated adsorption energy of −0.52 eV and −1.64 eV for HCrO4−, and −0.21 eV and −2.01 eV for Cr2O72−. The Al2O3 (aluminum oxide) and MnO (manganese oxide) embedded on the surface of dual-modified biochar bring more Cr(VI) absorption sites comparing to single-modified biochar, resulting in a maximum Cr(VI) saturated adsorption capacity of 152.86 mg g−1. The excellent removal performance is due to the synthetic effect of electrostatic attraction, reduction reaction, complexation reaction, and physical adsorption. The experimental results also indicated that the spontaneous adsorption process agreed well with the pseudo-second order and Langmuir models. This dual-modification strategy is not limited to the treatment of Cr(VI) with biochar, and may also be incorporated with the treatment of other heavy metals in aqueous environment.

Rare monogenic disorders such as lysosomal diseases have been at the forefront in the development of novel treatments where therapeutic options are either limited or unavailable. The increasing number of successful pre-clinical and clinical studies in the last decade demonstrates that gene therapy represents a feasible option to address the unmet medical need of these patients. This article provides a comprehensive overview of the current state of the field, reviewing the most used viral gene delivery vectors in the context of lysosomal storage disorders, a selection of relevant pre-clinical studies and ongoing clinical trials within recent years.

We provide microarray data comparing genome-wide differential expression and pathology throughout life in four lines of “amyloid” transgenic mice (mutant human APP, PSEN1, or APP/PSEN1) and “TAU” transgenic mice (mutant human MAPT gene). Microarray data were validated by qPCR and by comparison to human studies, including genome-wide association study (GWAS) hits. Immune gene expression correlated tightly with plaques whereas synaptic genes correlated negatively with neurofibrillary tangles. Network analysis of immune gene modules revealed six hub genes in hippocampus of amyloid mice, four in common with cortex. The hippocampal network in TAU mice was similar except that Trem2 had hub status only in amyloid mice. The cortical network of TAU mice was entirely different with more hub genes and few in common with the other networks, suggesting reasons for specificity of cortical dysfunction in FTDP17. This Resource opens up many areas for investigation. All data are available and searchable at http://www.mouseac.org.

Eucalyptus species are widely planted for reforestation in subtropical China. However, the effects of Eucalyptus plantations on the regional water use remain poorly understood. In an age sequence of 2-, 4- and 6-year-old Eucalyptus plantations, the tree water use and soil evaporation were examined by linking model estimations and field observations. Results showed that annual evapotranspiration of each age sequence Eucalyptus plantations was 876.7, 944.1 and 1000.7 mm, respectively, accounting for 49.81%, 53.64% and 56.86% of the annual rainfall. In addition, annual soil evaporations of 2-, 4- and 6-year-old were 318.6, 336.1, and 248.7 mm of the respective Eucalyptus plantations. Our results demonstrated that Eucalyptus plantations would potentially reduce water availability due to high evapotranspiration in subtropical regions. Sustainable management strategies should be implemented to reduce water consumption in Eucalyptus plantations in the context of future climate change scenarios such as drought and warming.

Concentrating solar power (CSP) station is counted as a promising flexible power supply when the net load power curve is duck-shaped in high photovoltaic (PV) penetration power system, which may lead to the serious phenomenon of PV curtailment and a large-capacity power shortage. This paper presents a mitigation strategy that replaces thermal power station with CSP station to participate in the optimal operation of power system for solving the duck-shaped net load power curve problem. The proposed strategy utilizes the dispatchability of thermal storage system (TSS) and the fast output regulation of unit in the CSP station. Simultaneously, considering the operation constraints of CSP station and network security constraints of the system, an optimization model is developed to minimize the overall cost including operation and penalty. The results obtained by nonlinear optimization function demonstrate that the replacement of concentrating solar power (CSP) station contributes to reducing the PV curtailment and lost load, while increasing the available equivalent slope for power balance. Thus, the proposed mitigation strategy can promote the penetration of PV generation and improve the flexibility of power system.

Fruit tree planting is a common practice for alleviating poverty and restoring degraded environment in developing countries. Yet, its environmental effects are rarely assessed. The Jiujushui watershed (261.4 km2), located in the subtropical Jiangxi Province of China, was selected to assess responses of several flow regime components on both reforestation and fruit tree planting. Three periods of forest changes, including a reference (1961 to 1985), reforestation (1986 to 2000) and fruit tree planting (2001 to 2016) were identified for assessment. Results suggest that the reforestation significantly decreased the average magnitude of high flow by 8.78%, and shortened high flow duration by 2.2 days compared with the reference. In contrast, fruit tree planting significantly increased the average magnitude of high flow by 27.43%. For low flows, reforestation significantly increased the average magnitude by 46.38%, and shortened low flow duration by 8.8 days, while the fruit tree planting had no significant impact on any flow regime components of low flows. We conclude that reforestation had positive impacts on high and low flows, while to our surprise, fruit tree planting had negative effects on high flows, suggesting that large areas of fruit tree planting may potentially become an important driver for some negative hydrological effects in our study area.

Forest change and climatic variability are two major drivers for influencing change in watershed hydrology in forest–dominated watersheds. Quantifying their relative contributions is important to fully understand their individual effects. This review paper summarizes the progress on quantifying the relative contributions of forest or land cover change and climatic variability to hydrology in large watersheds using available case studies. It compared pros and cons of various research methods, identified research challenges and proposed future research priorities. Our synthesis shows that the relative hydrological effects of forest changes and climatic variability are largely dependent on their own change magnitudes and watershed characteristics. In some severely disturbed watersheds, impacts of forest changes or land use changes can be as important as those from climatic variability. This paper provides a brief review on eight selected research methods for this type of research. Because each method or technique has its own strengths and weaknesses, combining two or more methods is a more robust approach than using any single method alone. Future research priorities include conducting more case studies, refining research methods, and considering mechanism-based research using landscape ecology and geochemistry approaches.

The laying down of memory requires strong stimulation resulting in specific changes in synaptic strength and corresponding changes in size of dendritic spines. Strong stimuli can also be pathological, causing a homeostatic response, depressing and shrinking the synapse to prevent damage from too much Ca2+ influx. But do all types of dendritic spines serve both of these apparently opposite functions? Using confocal microscopy in organotypic slices from mice expressing green fluorescent protein in hippocampal neurones, the size of individual spines along sections of dendrite has been tracked in response to application of tetraethylammonium. This strong stimulus would be expected to cause both a protective homeostatic response and long-term potentiation. We report separation of these functions, with spines of different sizes reacting differently to the same strong stimulus. The immediate shrinkage of large spines suggests a homeostatic protective response during the period of potential danger. In CA1, long-lasting growth of small spines subsequently occurs consolidating long-term potentiation but only after the large spines return to their original size. In contrast, small spines do not change in dentate gyrus where potentiation does not occur. The separation in time of these changes allows clear functional differentiation of spines of different sizes.

We derive explicit equations for all two-dimensional, semi-log-canonical hypersurface singularities by an elemetary method.

A multi-step annealing method was successfully applied to inclusions reduction and resistivity improvement of CdMnTe:In (CMT:In) single crystals with high resistivity, including a Cd atmosphere annealing step followed by a Te atmosphere annealing step. After the Cd atmosphere annealing step, the density of Te inclusions was reduced distinctly, and it could be also decreased in the subsequent step of re-annealing under Te atmosphere. Both the resistivity and IR transmittance decreased notably after Cd atmosphere annealing, whereas they increased tremendously after re-annealing under a Te atmosphere. The reduction of full-width at-half-maximum (FWHM) and the increase of the intensity of the X-ray rocking curve indicated an improvement of the crystal quality. Meanwhile, after Cd atmosphere annealing, the increase of the intensity of the (D0,X) peak and the disappearance of the (A0,X) peak in photoluminescence (PL) measurements suggested further that the crystal quality was improved. The detector performance was enhanced obviously after annealing. The higher the annealing temperature, the better the performance was. The detector fabricated by CMT:In slice (Cd atmosphere annealing at 1073 K for 240 h and Te atmosphere re-annealing at 773 K for 120 h) with 9.43% energy resolution and 1.25 × 10−3 cm2/V μτ value had the best detector performance.

Objective: Rare disease Background: Diffuse intestinal lipomatosis is a rare condition that infiltrates mature fatty tissue into the intestinal submucosa and subserosa of the small or large intestine and can present with intestinal obstruction or torsion. This report is of the case of a 58-year-old woman who had acute torsion of the small bowel due to diffuse small intestinal lipomatosis. Case Report: A 58-year-old woman, who was otherwise in good health, arrived at our Emergency Department experiencing sudden, intense pain in the lower abdomen. She also reported abdominal swelling, feelings of nausea, vomiting, and reduced ability to defecate for at least 2 days. The next morning, contrast-enhanced abdominal computed tomography (CT) scan was performed, showing diffuse thickening of the small intestinal wall with hypodensity, fatty density, lumen narrowing, and wall thinning. The small intestine demonstrated a whirlpool-like distribution in the lower right abdomen and localized thickening of the small intestinal wall, suggesting acute intestinal torsion. An hour later, an emergency operation was performed to remove part of the small intestine. Three days later, pathological results showed a thin intestinal wall, expansion of the mucosal layer and submucosa, and hyperplasia of adipose tissue. Conclusions: This report presents a rare case of torsion and small bowel obstruction caused by diffuse intestinal lipomatosis and focuses on the abdominal enhanced CT scan, which showed diffuse thickening of the small intestine, with multiple areas of fat density and torsion of the small intestine in the right lower abdomen. Histopathology is also presented, with the result showing intestinal lipomatosis. [ABSTRACT FROM AUTHOR]

Branchiostoma belcheri tsingtauense is an important species to study the evolution of chordates and has important scientific value. Based on the survey data, the effect of sediment environment on the habitat density of Branchiostoma belcheri tsingtauense were studied in Changli Nature Reserve in spring (May) and summer (August) of 2017. The resuits showed that Branchiostoma belcheri tsingtauense mainly distributed in sandy sediment in the study area. The median particle size ranged from 200 to 300 pm. When the sulfide content in sediment was below 60 mg/kg and the organic carbon content was between 0.03 and 0.1%, Branchiostoma belcheri tsingtauense was more favorable for survival and reproduction. [ABSTRACT FROM AUTHOR]

Understanding hydrological responses to reforestation is an important subject in watershed management, particularly in large forested watersheds (>1000 km²). In this study, we selected two large forested watersheds (Pingjiang and Xiangshui) located in the upper reach of the Poyang Lake watershed, southeastern China (with an area of 3261.4 and 1458 km², respectively), along with long-term data on climate and hydrology (1954-2006) to assess the effects of large-scale reforestation on streamflow. Both watersheds have similar climate and experienced comparable and dramatic forest changes during the past decades, but with different watershed properties (e.g., the topography is much steeper in Xiangshui than in Pingjiang), which provides us with a unique opportunity to compare the differences in hydrological recovery in two contrasted watersheds. Streamflow at different percentiles (e.g., 5, 10, 50 and 95%) were compared using a combination of statistical analysis with a year-wise method for each watershed. The results showed that forest recovery had no significant effects on median flows (Q50%) in both watersheds. However, reforestation significantly reduced high flows in Pingjiang, but had limited influence in Xiangshui. Similarly, reforestation had significant and positive effects on low flows (Q95%) in Pingjiang, while it did not significantly change low flows in Xiangshui. Thus, hydrological recovery is limited and slower in the steeper Xiangshui watershed, highlighting that watershed properties are also important for determining hydrological responses to reforestation. This finding has important implications for designing reforestation and watershed management strategies in the context of hydrological recovery. [ABSTRACT FROM AUTHOR]

Understanding hydrological responses to reforestation is an important subject in watershed management, particularly in large forested watersheds (>1000 km²). In this study, we selected two large forested watersheds (Pingjiang and Xiangshui) located in the upper reach of the Poyang Lake watershed, Southeastern China (with an area of 3261.4 and 1458 km², respectively) to assess the effects of large-scale reforestation on streamflow. Both watersheds have similar climate and experienced comparable and dramatic forest changes during the past decades, but with contrasted watershed properties (e.g., the topography is much steeper in Xiangshui than in Pingjiang), which provides us with a unique opportunity to compare the differences in hydrological recovery in two contrasted watersheds. Streamflow at different percentiles (e.g., 5%, 10%, 50% and 95%) were compared using a combination of statistical analysis with year-wise method for each watershed. The results showed that forest recovery had no significant effects on median flows (Q50%) in both watersheds. However, reforestation significantly reduced high flows in Pingjiang, but had limited influence in Xiangshui. Similarly, reforestation had significant and positive effects on low flows (Q95%) in Pingjiang, while it did not significantly change low flows in Xiangshui. Thus, hydrological recovery is limited and slower in the steeper Xiangshui watershed, highlighting that watershed property is also important for determining hydrological responses to reforestation. This finding has important implications for designing reforestation and watershed management strategies in the context of hydrological recovery. [ABSTRACT FROM AUTHOR]

Assessing how forest disturbance and climate change affect baseflow or groundwater discharge is critical for understanding water resource supply and protecting aquatic functions. Previous studies have mainly evaluated the effects of forest disturbance on streamflow, with rare attention on baseflow, particularly in large watersheds. However, studying this topic is challenging as it requires explicit inclusion of climate into assessment due to their interactions at any large watersheds. In this study, we used Upper Similkameen River watershed (USR) (1810 km²), located in the southern interior of British Columbia, Canada to examine how forest disturbance and climate variability affect baseflow. The conductivity mass balance method was first used for baseflow separation, and the modified double mass curves were then employed to quantitatively separate the relative contributions of forest disturbance and climate variability to annual baseflow. Our results showed that average annual baseflow and baseflow index (baseflow/streamflow) were about 85.2 ± 21.5 mm year-1 and 0.22 ± 0.05 for the study period of 1954-2013, respectively. The forest disturbance increased the annual baseflow of 18.4 mm, while climate variability decreased 19.4 mm. In addition, forest disturbance also shifted the baseflow regime with increasing of the spring baseflow and decreasing of the summer baseflow. We conclude that forest disturbance significantly altered the baseflow magnitudes and patterns, and its role in annual baseflow was equal to that caused by climate variability in the study watershed despite their opposite changing directions. The implications of our results are discussed in the context of future forest disturbance (or land cover changes) and climate changes. [ABSTRACT FROM AUTHOR]

We study the geography of Gorenstein stable log surfaces and prove two inequalities for their invariants: the stable Noether inequality and the P2-inequality. By constructing examples we show that all invariants are realised except possibly some cases where the inequalities become equalities. [ABSTRACT FROM AUTHOR]

A straightforward and concise method for the highly stereoselective synthesis of α,β-unsaturated hydrazones by the Y(OTf)3-catalyzed cascade propargylic substitution/aza-Meyer-Schuster rearrangement reaction of tertiary propargylic alcohols and p-toluenesulfonyl hydrazide under an air atmosphere is developed. A series of α,β-unsaturated hydrazones have been synthesized from simple and readily available starting materials in good yields. Furthermore, the obtained α,β-unsaturated hydrazones are converted into pyrazoles in the presence of LiOt-Bu. [ABSTRACT FROM AUTHOR]

Detecting and treating Alzheimer's disease, before cognitive deficits occur, has become the health challenge of our time. The earliest known event in Alzheimer's disease is rising amyloid-β. Previous studies have suggested that effects on synaptic transmission may precede plaque deposition. Here we report how relative levels of different soluble amyloid-β peptides in hippocampus, preceding plaque deposition, relate to synaptic and genomic changes. Immunoprecipitation-mass spectrometry was used to measure the early rise of different amyloid-β peptides in a mouse model of increasing amyloid-β ('TASTPM', transgenic for familial Alzheimer's disease genes APP/PSEN1). In the third postnatal week, several amyloid-b peptides were above the limit of detection, including amyloid-β40, amyloid-β38 and amyloid-β42 with an intensity ratio of 6:3:2, respectively. By 2 months amyloid-β levels had only increased by 50% and although the ratio of the different peptides remained constant, the first changes in synaptic currents, compared to wild-type mice could be detected with patch-clamp recordings. Between 2 and 4 months old, levels of amyloid-β40 rose by ~7-fold, but amyloid-β42 rose by 25-fold, increasing the amyloid-β42:amyloid-β40 ratio to 1:1. Only at 4 months did plaque deposition become detectable and only in some mice; however, synaptic changes were evident in all hippocampal fields. These changes included increased glutamate release probability (P < 0.001, n = 7-9; consistent with the proposed physiological effect of amyloid-β) and loss of spontaneous action potential-mediated activity in the cornu ammonis 1 (CA1) and dentate gyrus regions of the hippocampus (P < 0.001, n = 7). Hence synaptic changes occur when the amyloid-β levels and amyloid-β42:amyloid-β40 ratio are still low compared to those necessary for plaque deposition. Genome-wide microarray analysis revealed changes in gene expression at 2-4 months including synaptic genes being strongly affected but often showing significant changes only by 4 months. We thus demonstrate that, in a mouse model of rising amyloid-β, the initial deposition of plaques does not occur until several months after the first amyloid-β becomes detectable but coincides with a rapid acceleration in the rise of amyloid-β levels and the amyloid-β42:amyloid-β40 ratio. Prior to acceleration, however, there is already a pronounced synaptic dysfunction, reflected as changes in synaptic transmission and altered gene expression, indicating that restoring synaptic function early in the disease progression may represent the earliest possible target for intervention in the onset of Alzheimer's disease. [ABSTRACT FROM AUTHOR]